Dosage forms comprising abiraterone acetate

Abstract

Disclosed are solid oral dosage forms comprising about 500 mg of abiraterone acetate; and a film coating that is positioned on an outer surface of said dosage form, wherein the dosage forms are bioequivalent to 250 mg ZYTIGA® abiraterone acetate dosage forms when administered orally on an equivalent dose basis. Also disclosed are approved drug products comprising 500 mg abiraterone acetate, as are methods of treatment, of reducing pill burden, and of providing pharmaceutical regimen that is bioequivalent to 250 mg ZYTIGA® abiraterone acetate dosage forms when administered orally on an equivalent dose basis.

What is claimed: 
     
         1 . A solid oral dosage form comprising about 500 mg of abiratirone acetate and having a dissolution profile characterized by one or more of features (a)-(f):
 (a) about 43% of said dosage form dissolves after five minutes;   (b) about 71% of said dosage form dissolves after 10 minutes;   (c) about 88% of said dosage form dissolves after 20 minutes;   (d) about 94% of said dosage form dissolves after 30 minutes;   (e) about 98% of said dosage form dissolves after 45 minutes; and,   (f) about 99% of said dosage form dissolves after 60 minutes,   
       when measured by the USP 2 Paddle method at 75 rpm in 900 mL of an aqueous solution comprising 56.5 mM phosphate buffer with 0.25% (w/v) sodium lauryl sulfate at pH 4.5 and a temperature of 37.0±0.5° C. 
     
     
         2 . A solid oral dosage form comprising about 500 mg of abiratirone acetate and having a dissolution profile characterized by one or more of features (a)-(f):
 (a) about 31% of said dosage form dissolves after five minutes;   (b) about 65% of said dosage form dissolves after 10 minutes;   (c) about 94% of said dosage form dissolves after 20 minutes;   (d) about 98% of said dosage form dissolves after 30 minutes;   (e) about 99% of said dosage form dissolves after 45 minutes; and,   (f) about 99% of said dosage form dissolves after 60 minutes,   
       when measured by the USP 2 Paddle method at 75 rpm in 900 mL of an aqueous solution comprising 56.5 mM phosphate buffer with 0.25% (w/v) sodium lauryl sulfate at pH 4.5 and a temperature of 37.0±0.5° C. 
     
     
         3 . A solid oral dosage form comprising:
 about 500 mg of abiraterone acetate; and   a film coating that is positioned on an outer surface of said dosage form,   
       wherein said dosage forms are bioequivalent, when administered orally on an equivalent dose basis, to 250 mg ZYTIGA® abiraterone acetate dosage forms. 
     
     
         4 . The dosage form according to  claim 1  comprising about 30 to about 50 wt % of said abiraterone acetate. 
     
     
         5 . The dosage form according to  claim 4  comprising about 35 to about 45 wt % of said abiraterone acetate. 
     
     
         6 . The dosage form according to  claim 5  comprising about 35 wt % of said abiraterone acetate. 
     
     
         7 . The dosage form according to  claim 5  comprising about 45 wt % of said abiraterone acetate. 
     
     
         8 . The dosage form according to  claim 1  further comprising one or more of a diluent, a disintegrant, a binder, a surfactant, a glidant, or a lubricant. 
     
     
         9 . The dosage form according to  claim 2  further comprising a diluent, a disintegrant, a binder, a surfactant, a glidant, and a lubricant. 
     
     
         10 . The dosage form according to  claim 8  further comprising a diluent that is selected from lactose monohydrate, microcrystalline cellulose, and silicified microcrystalline cellulose. 
     
     
         11 . The dosage form according to  claim 8  further comprising a disintegrant, wherein said disintegrant is croscarmellose sodium. 
     
     
         12 . The dosage form according to  claim 8  further comprising a binder that is selected from povidone and hypromellose. 
     
     
         13 . The dosage form according to  claim 8  further comprising a surfactant, wherein said surfactant is sodium lauryl sulfate. 
     
     
         14 . The dosage form according to  claim 8  comprising lactose monohydrate, microcrystalline cellulose or silicified microcrystalline cellulose, croscarmellose sodium, povidone or hypromellose, sodium lauryl sulfate, colloidal silicon dioxide, and magnesium stearate. 
     
     
         15 . The dosage form according to  claim 14  comprising about 22-28 wt % lactose monohydrate, about 16-17 wt % microcrystalline cellulose or about 18-20 wt % silicified microcrystalline cellulose, about 6-7 wt % croscarmellose sodium, about 4-6 wt % povidone or about 1-2 wt % hypromellose, about 4-6 wt % sodium lauryl sulfate, about 0.5-1.5 wt % colloidal silicon dioxide, and about 1-2 wt % magnesium stearate. 
     
     
         16 . The dosage form according to  claim 15 , wherein said dosage form comprises about 35 wt % abiraterone acetate, about 28 wt % lactose monohydrate, about 20 wt % silicified microcrystalline cellulose, about 6 wt % croscarmellose sodium, about 5 wt % povidone, about 1 wt % colloidal silicon dioxide, and about 1.5 wt % magnesium stearate, wherein the combination of each of said components in the dosage form equals 100 wt %. 
     
     
         17 . The dosage form according to  claim 15 , wherein said dosage form comprises about 45 wt % abiraterone acetate, about 23 wt % lactose monohydrate, about 17 wt % microcrystalline cellulose, about 6 wt % croscarmellose sodium, about 2 wt % hypromellose, about 1 wt % colloidal silicon dioxide, and about 1.5 wt % magnesium stearate, wherein the combination of each of said components in the dosage form equals 100 wt %. 
     
     
         18 . The dosage form according to  claim 1 , wherein two of said dosage forms administered orally at substantially the same time exhibit a C max  of about 130 ng/mL. 
     
     
         19 . The dosage form according to  claim 1 , wherein two of said dosage forms administered orally at substantially the same time exhibit a C max  of about 108 ng/mL. 
     
     
         20 . The dosage form according to  claim 1 , wherein two of said dosage forms administered orally at substantially the same time exhibit a t max  at about 2.0 hours. 
     
     
         21 . The dosage form according to  claim 1 , wherein two of said dosage forms administered orally at substantially the same time exhibit an area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC last ) of about 679 ng*h/mL. 
     
     
         22 . The dosage form according to  claim 1 , wherein two of said dosage forms administered orally at substantially the same time exhibit an area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC last ) of about 589 ng*h/mL. 
     
     
         23 . The dosage form according to  claim 1 , wherein two of said dosage forms administered orally at substantially the same time exhibit an area under the plasma concentration-time curve extrapolated to infinite time (AUC ∞ ) of about 707 ng*h/mL. 
     
     
         24 . The dosage form according to  claim 1 , wherein two of said dosage forms administered orally at substantially the same time exhibit an area under the plasma concentration-time curve extrapolated to infinite time (AUC ∞ ) of about 600 ng*h/mL. 
     
     
         25 . The dosage form according to  claim 1 , wherein two of said dosage forms administered orally at substantially the same time exhibit an apparent terminal elimination half-life (t 1/2 ) of about 18.6 hours. 
     
     
         26 . The dosage form according to  claim 1 , wherein two of said dosage forms administered orally at substantially the same time exhibit an apparent terminal elimination half-life (t 1/2 ) of about 18.1 hours. 
     
     
         27 . A method of reducing pill burden on a subject in need of an abiraterone acetate pharmaceutical regimen comprising orally administering to a subject two dosage forms according to  claim 1  at substantially the same time. 
     
     
         28 . A method of treating a subject using an abiraterone acetate pharmaceutical regimen that is bioequivalent to 250 mg ZYTIGA® abiraterone acetate dosage forms when administered orally on an equivalent dose basis, comprising orally administering a dosage form according to  claim 27 . 
     
     
         29 . A method of treating a subject who has prostate cancer comprising orally administering to said subject a dosage form according to  claim 1 . 
     
     
         30 . The method according to  claim 29  comprising orally administering to said subject two of said dosage forms at substantially the same time. 
     
     
         31 . A method of selling a drug product comprising abiraterone acetate, said method comprising selling such drug product, wherein a drug product label for a reference listed drug for such drug product includes instructions for treating non-metastatic castration resistant prostate cancer. 
     
     
         32 . The method of  claim 31 , wherein the drug product is an ANDA drug product, a supplemental New Drug Application drug product or a 505(b)(2) drug product. 
     
     
         33 . A method of offering for sale a drug product comprising abiraterone acetate, said method comprising offering for sale such drug product, wherein a drug product label for a reference listed drug for such drug product includes instructions for treating non-metastatic castration resistant prostate cancer. 
     
     
         34 . The method of  claim 33 , wherein the drug product is an ANDA drug product, a supplemental New Drug Application drug product or a 505(b)(2) drug product. 
     
     
         35 . A method of selling a drug product comprising abiraterone acetate, said method comprising selling such drug product, wherein the drug product label for a reference listed drug for such drug product comprises metastasis free survival data. 
     
     
         36 . The method of  claim 35 , wherein the metastasis free survival data for abiraterone acetate in combination with androgen deprivation therapy arm has a median of about 40.5 months. 
     
     
         37 . A method of offering for sale a drug product comprising abiraterone acetate, said method comprising offering for sale such drug product, wherein the drug product label for a reference listed drug for such drug product comprises metastasis free survival data. 
     
     
         38 . The method of  claim 37 , wherein the metastasis free survival data for abiraterone acetate in combination with androgen deprivation therapy arm has a median of about 40.5 months. 
     
     
         39 . An approved drug product comprising 500 mg abiraterone acetate. 
     
     
         40 . An approved drug product of  claim 39 , wherein the approved drug product is a NDA drug product, an ANDA drug product, a supplemental New Drug Application drug product, or a 505(b)(2) drug product. 
     
     
         41 . An approved drug product of  claim 39 , wherein a reference listed drug product for the approved drug product includes a drug product label. 
     
     
         42 . An approved drug product of  claim 41 , wherein the drug product label comprises metastasis free survival data.